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心肌相关转录因子A调控祖细胞向米色脂肪细胞的转化。

Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes.

作者信息

McDonald Meghan E, Li Chendi, Bian Hejiao, Smith Barbara D, Layne Matthew D, Farmer Stephen R

机构信息

Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

出版信息

Cell. 2015 Jan 15;160(1-2):105-18. doi: 10.1016/j.cell.2014.12.005. Epub 2015 Jan 8.

DOI:10.1016/j.cell.2014.12.005
PMID:25579684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4384505/
Abstract

Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develops within white adipose tissue in response to physiological stimuli; however, the developmental origin of these "brite" or "beige" adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin-related transcription factor A, MRTFA. White adipose tissue from MRTFA(-/-) mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA(-/-) mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes.

摘要

脂肪组织是代谢稳态的重要调节者。与以甘油三酯形式储存多余能量的白色脂肪组织不同，棕色脂肪组织具有产热功能，通过线粒体解偶联蛋白UCP1的独特表达将能量以热量形式散发。一部分UCP1+脂肪细胞会在白色脂肪组织内响应生理刺激而形成；然而，这些“亮”或“米色”脂肪细胞的发育起源尚不清楚。在此，我们报告鉴定出一条BMP7-ROCK信号轴，该信号轴通过控制G-肌动蛋白调节的转录共激活因子心肌素相关转录因子A（MRTFA）来调节米色脂肪细胞的形成。来自MRTFA（-/-）小鼠的白色脂肪组织含有更多的多泡脂肪细胞，并表达更高水平的棕色特异性蛋白，包括UCP1。MRTFA（-/-）小鼠还表现出改善的代谢状况，并对饮食诱导的肥胖和胰岛素抵抗具有保护作用。因此，我们的研究揭示了一条驱动具有生理功能的米色脂肪细胞发育的核心途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90e3/4384505/65305904b88e/nihms-646781-f0007.jpg
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